title: Do radiographic joint damage and disease activity influence functional disability through different mechanisms? Direct and indirect effects of disease activity in established rheumatoid arthritis.
abstract: OBJECTIVE
  To explore the relationship between rheumatoid arthritis (RA) disease activity and functional disability over time, considering indirect (predictive) and direct (concurrent) associations as well as the influence of radiographic joint damage and treatment strategy.
  
  
  METHODS
  Functional disability [Health Assessment Questionnaire (HAQ)], disease activity [28-joint Disease Activity Score (DAS28)], and radiographic joint damage [Sharp/van der Heijde score (SHS)] were measured in 4 consecutive randomized controlled trials with increasingly intensive (tight control) treatment strategies. Average followup time for the 3 cohorts was 97, 53, and 50 months, respectively. Next to current DAS28, the previous DAS28 was used to study the predictive effect of a change in DAS28 on progression of functional disability (HAQ). Finally, it was investigated whether SHS mediated the predictive effect of DAS28.
  
  
  RESULTS
  In patients treated with intensive treatment strategies, the progression of HAQ over time was statistically significantly less (p < 0.0001). The predictive influence of DAS28 on HAQ progression increased over the duration of the disease. SHS was not found to influence HAQ progression and did not mediate the predictive effect of DAS28. In the less intensively treated patients, the direct effect of disease activity decreased with disease duration, and contrarily, SHS did influence HAQ progression, but was not found to (fully) mediate the predictive effect of DAS28.
  
  
  CONCLUSIONS
  In patients with RA treated with modern treatment strategies, there is less functional decline over time. Further, disease activity does predict functional decline but joint damage does not. This might indicate that factors associated with cumulative disease activity but not visible on radiographs can influence functional decline in patients with RA. This further underlines the importance of disease activity as a treatment target in early RA and in established RA.
authors.affiliation: From the Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands. S.C.Nair@umcutrecht.nl
authors.forename: Sandhya C
authors.initials: SC
authors.lastname: Nair
authors.forename: Johannes W J
authors.initials: JW
authors.lastname: Bijlsma
authors.forename: Jacobien H
authors.initials: JH
authors.lastname: van der Werf
authors.forename: Maaike J
authors.initials: MJ
authors.lastname: van der Veen
authors.forename: Suzanne P
authors.initials: SP
authors.lastname: Linn-Rasker
authors.forename: Simone
authors.initials: S
authors.lastname: Vreugdenhil
authors.forename: Floris P J G
authors.initials: FP
authors.lastname: Lafeber
authors.forename: Paco M J
authors.initials: PM
authors.lastname: Welsing
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000503:physiopathology; D001175:Arthrography; D004185:Disability Evaluation; D018450:Disease Progression; D005260:Female; D006801:Humans; D007596:Joints / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D008962:Models, Theoretical; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents
keywords: DISEASE ACTIVITY; FUNCTIONAL DISABILITY; RADIOGRAPHIC JOINT DAMAGE; RHEUMATOID ARTHRITIS